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With New Data, Amgen Promises Refund If Cholesterol Drug Doesn’t Work

Stung by slow sales of its next-generation anti-cholesterol drug, Amgen hopes new clinical data, released this morning, will spur doctors to boost prescriptions and—perhaps more important—drive insurers to loosen their restrictions.

The data, from a massive study of more than 27,000 patients, come at a time when drug and healthcare prices are a top U.S. political issue, and pricey new cholesterol drugs have been a key battleground.

With the data, Amgen (NASDAQ: AMGN) is providing the first significant evidence that evolocumab (Repatha), part of a new wave of drugs called PCSK9 inhibitors, can reduce the rates of heart attacks and strokes. In 2015, the FDA approved evolocumab as well as a rival PCSK9 inhibitor based on evidence that they lowered cholesterol.

Sekar Kathiresan, director of preventative cardiology at Massachusetts General Hospital in Boston, called the results “practice-changing.” But he nonetheless added there “will still be a vigorous debate about cost-effectiveness.”

No one disputes that heart disease is a major medical problem. The current standard of care, a class of drugs called statins, are seemingly everywhere, but heart disease remains the leading cause of death in the U.S., according to the Centers for Disease Control and Prevention.

But how much society is willing to pay for better treatments has become a key national issue. The data from Amgen’s “Fourier” study are meant to prove to insurers and clinicians that evolocumab is worth its $14,000 per month list price, which was met with major resistance. Evolocumab generated $141 million in revenue in 2016, well short of initial expectations. The rival drug, alirocumab (Praluent), fared about as badly, with $116 million in 2016 sales.

Amgen said today it would offer a refund to payers that “lower access barriers” if patients on their plans taking evolocumab suffer a heart attack or stroke. Specifically, for any patient who had a heart attack or stroke after taking evolocumab for at least six months, payers would get a refund in the form of an additional rebate, the details of which would be subject to negotiations with each payer.

The company hinted at price flexibility when evolocumab launched, and already uses payment schemes that link the drug’s net price to cholesterol reductions and “anticipated appropriate patient utilization.” But this is the first time the firm has linked refunds to health setbacks. Cardiologists are taking a wait and see approach for now.

“I’ve never really seen [alternative pricing models] pan out as a winner in the clinic,” said Eric Topol, a practicing cardiologist and the head of the Scripps Translational Science Institute. “I don’t hold a lot of hope.”

Amgen released the first and most important batch of Fourier data today at the American College of Cardiology’s annual meeting. The detailed results are being published simultaneously in the New England Journal of Medicine. Here are the headline numbers:

After a median of 2.2 years of treatment, 1,344 (or 9.8 percent) of the patients treated with a combination of statins and evolocumab suffered heart attacks, strokes, cardiovascular deaths, or were hospitalized for unstable angina or bypass surgery. By comparison, 1,563 patients (11.3 percent) of those on treatment with a statin alone suffered those events—a 15 percent difference in relative risk of such events between the two groups, and an absolute risk reduction of 1.5 percent for the combination treatment. Measuring the difference in all of these events was the study’s main goal.

A secondary measure only included patients who had suffered heart attacks, strokes, or cardiovascular deaths. By this measure, 816 (or 5.9 percent) of the patients treated with a combination of statins and evolocumab suffered heart attacks, strokes, or cardiovascular deaths, compared to 1,013 (7.4 percent) for those on treatment with a statin alone—a 20 percent difference in relative risk of such events between the two groups, and an absolute risk reduction of 1.5 percent, again, for the combination.

More data on safety and the restricted access to the drug are coming later this weekend, but Amgen reported, top-line, that no new safety problems cropped up during the trial. Cardiologists not associated with Amgen had flagged two key indicators to watch: rates of neurological side events (1.6 percent for evolocumab patients, 1.5 percent for statin-only), and the onset of diabetes (8.1 percent for evolocumab, 7.7 percent for statin-only).

While Amgen said in a statement that those differences weren’t notable, Topol disagreed, and said that the increase in instances of diabetes partially offsets evolocumab’s reduction in heart attacks. “The [diabetes] signal is there,” he said. “The study just isn’t powered enough to show that it’s statistically significant.”

Still, Elliott Levy, Amgen’s senior vice president of global development, said the study results were “about as good a result as you can get.”

“I can’t think of any intervention in cardiovascular medicine that had a treatment effect of 20 percent or more on major cardiovascular events with this kind of safety profile that has not been incorporated into guidelines or changed practice,” he said.

Levy noted that the treatment effect got better with time—a 16 percent reduction in heart attacks, strokes, and deaths climbed to 25 percent after one year. The implication, he said, is that larger benefit is “probably a true reflection of what patients will experience if they take the drug over time.”

“So we expect that this drug also will be embraced by the medical community” and incorporated into clinical guidelines, Levy said. “Then it will be up to the payers to accommodate the drug.”